International Journal of Surgery 33 (2016) 237e241

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International Journal of Surgery

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Review

Direct Peritoneal Resuscitation: A review

Jessica L. Weaver a, b, *, Jason W. Smith a
a
University of Louisville Department of Surgery, Louisville, KY, USA
b
Robley Rex Veterans Administration Hospital, Louisville, KY, USA

h i g h l i g h t s

Direct Peritoneal Resuscitation (DPR) instills hypertonic solution into the abdomen in addition to IV resuscitation.

DPR causes rapid vasodilation and improves visceral organ blood flow after shock.

DPR reduces edema and allows earlier abdominal closure after damage control surgery.

DPR reduces serum levels of inflammatory cytokines and other mediators.

DPR increases the number of organs procured per donor after acute brain death.

a r t i c l e i n f o a b s t r a c t

Article history: Conventional treatment for hemorrhagic shock includes the infusion of intravenous (IV) fluid and blood
Received 1 July 2015 products in order to restore intravascular volume. However, even after normal heart rate and blood
Received in revised form pressure are restored, the visceral organs often remain ischemic. This leads to organ dysfunction and also
24 August 2015
releases numerous cytokines and inflammatory mediators which activate the body's inflammatory
Accepted 2 September 2015
response. The use of Direct Peritoneal Resuscitation (DPR) helps counteract this response. DPR involves
Available online 16 September 2015
infusion of hypertonic fluid into the abdomen in addition to IV resuscitation. This causes rapid and
sustained dilation of the arterioles, especially those in the intestine, which reduces organ ischemia and
Keywords:
Direct Peritoneal Resuscitation
cellular hypoxia. Studies in animals have demonstrated that use of DPR after hemorrhagic shock can
Shock reduce organ edema, improve liver blood flow, and reduce serum levels of inflammatory cytokines.
Inflammation Subsequent human studies have shown that DPR after damage control surgery for hemorrhage or sepsis
Hemorrhage leads to faster abdominal closure, higher rate of primary fascial closure, and reduced abdominal com-
Brain death plications. Peritoneal resuscitation has also shown benefits in the resuscitation after acute brain death,
Visceral ischemia including reduced inflammatory mediators and organ edema. Use of DPR in potential organ donors leads
to an increase in the number of organs procured per donor, most frequently by increasing the number of
lungs procured.
© 2015 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

1. Background the pulmonary and systemic circulation. Even after normalization

Severe traumatic injury can lead to hemorrhagic shock. The
traditional treatment for significant hemorrhage is the adminis-
tration of intravenous (IV) crystalloid solutions as well as blood
products to restore intravascular volume [1]. However, despite
resuscitation that restores heart rate and blood pressure to normal,
patients can still progress to organ dysfunction. In response to
shock, the body experiences a profound vasoconstriction of both
* Corresponding author. 550 S Jackson St, ACB 2nd Floor Rm A2J19, Louisville, KY
40202, USA.
E-mail address: jlweav08@louisville.edu (J.L. Weaver).
of hemodynamics, this vasoconstriction resolves slowly, possibly
due to the intense catecholamine surge and sympathetic response
that accompanies trauma and hemorrhage [2]. The visceral organs
such as the small intestine and liver are particularly prone to pro-
longed ischemia as the body shunts blood to more vital organs such
as the brain, heart, and kidneys [3,4].
This prolonged hypoperfusion of the intestine can precipitate a
severe prolonged inflammatory response due to mobilization of
Damage-associated molecular pattern molecules (DAMPs) from
ischemic tissue [5]. Additionally, hypovolemic shock has been
demonstrated to cause sloughing of the intestinal mucosa and
increased intestinal permeability. This is associated with decreased
function of tight junctions between endothelial cells [6]. This

http://dx.doi.org/10.1016/j.ijsu.2015.09.037
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238 J.L. Weaver, J.W. Smith / International Journal of Surgery 33 (2016) 237e241
increased permeability of the bowel wall allows bacteria by-
products to translocate out of the bowel lumen. It has also been
demonstrated that even a short period of intestinal ischemia leads
to activation of inflammatory cytokines and other mediators [4].
Efforts to develop antagonists for specific inflammatory mediators
have thus far been unsuccessful in clinical studies, and fail to
address the root of the problem of global tissue ischemia and
inflammation [7]. Thus, our work attempts to reverse the intestinal
hypoperfusion that is the underlying cause of inflammation and
organ dysfunction after shock.
2. Initial microcirculatory studies
Peritoneal dialysis (PD) fluid causes visceral vasodilation. This is
thought to be due to the hypertonicity of the fluid, as well as the
lactate, glucose, and glucose degradation products contained
within the fluid [8]. Our initial microcirculatory studies directly
examined the effects of PD fluid application to the terminal ileum,
and demonstrated that all levels of visceral arterioles rapidly
dilated when exposed to hypertonic fluid (see Fig. 1) but did not
respond to isotonic solution [9]. These observations suggested that
infusion of a hypertonic solution into the abdomen during periods
of low intestinal blood flow, such as during hemorrhagic or septic
shock, could help maintain blood flow to the visceral organs. This
novel resuscitation was dubbed Direct Peritoneal Resuscitation
(DPR).
The hypertonicity of solution appears to reduce transcellular
water diffusion through the aquaporin channels of cells following
ischemia. This serves to maintain blood flow to the abdominal or-
gans, by reducing endothelial cell swelling and maintaining capil-
lary bed cross sectional area during and after resuscitation, leading
to better tissue blood flow and reduced cellular ischemia. Use of
adjunctive DPR preserves endothelial cell function when compared
to conventional resuscitation [10]. DPR also prevents the significant
visceral edema via the same mechanism leading to better cellular
function and reduced edema produced cellular dysfunction.
Microscopic evidence points toward a preservation of organ and
cellular architecture following shock in patients treated with DPR
compared to those treated with conventional resuscitation tech-
niques alone [11].
3. Animal model
To better examine the use of DPR in vivo we utilized an animal
model for hemorrhagic shock, and subsequently for acute brain
death. The hemorrhagic shock model used male SpragueeDawley
Fig. 1. Percent change in diameter of different levels of arterioles when treated with
Delflex solution vs solutions of differing pH.
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rats. The animals were anesthetized and then underwent trache-
ostomy and cannulation of the carotid artery, internal jugular vein,
and femoral artery and vein. Hemorrhage was induced with blood
withdrawal to mean arterial pressure (MAP) of 40% baseline for
60 min. Rats were resuscitated with blood and saline with or
without intraperitoneal injection of Delflex solution. Animals were
sacrificed four hours after resuscitation was complete. The acute
brain death (ABD) model began similarly, but after the vascular
cannulas were inserted a 4F angiocatheter was inserted into the
epidural space and inflated to induce intracranial hypertension and
ultimately brain death. Animals were then resuscitated with IV
saline with or without DPR.
4. DPR improves organ blood flow
In the hemorrhage model, MAP responded to resuscitation and
returned to pre-hemorrhage levels in both conventional resusci-
tation (CR) and DPR animals [7,10,12]. Similarly, liver blood flow
returned to normal in CR and DPR groups after resuscitation.
However, in the CR group, liver blood flow begins to fall as soon as
resuscitation was complete (Fig. 2). The addition of DPR prevented
this decrease [11]. Using colorimetric microspheres we demon-
strated that the addition of DPR improves blood flow to the
jejunum, ileum, spleen, pancreas, lung, and skeletal muscle [12].
In the ABD model, brain death is signaled by a sympathetic surge
marked by high blood pressure and heart rate, followed by pro-
found hypotension as sympathetic tone is lost. Ongoing resuscita-
tion is required to maintain blood pressure in these patients. In our
ABD experiments use of high levels of IV fluid (IVF) improved heart
rate, MAP, and mortality compared to low levels of IVF resuscita-
tion. Use of DPR achieved similar results while requiring much less
total IVF. The addition of DPR also significantly increased liver blood
flow and correlated with the lower levels of alanine transaminase
and alkaline phosphatase [13].
5. DPR reduces organ edema and tissue necrosis
In the hemorrhage model, histologic examination demonstrated
that CR animals had significant edema in the liver (see Fig. 3) and
sloughing of the villi and loss of intestinal crypts in the ileum. The
DPR animals showed significantly reduced tissue damage and
better preservation of cellular architecture [11]. In the ABD model
the high IVF group was the most like the DPR group in terms of
outcome. However, examination of the lung, liver, and ileum
demonstrated significantly more edema in all three organs in the
IVF only group when compared to the DPR group [13].
6. DPR reduces serum inflammatory cytokines and DAMPs
The fact that effects of DPR extend to organs beyond the
abdominal cavity suggests that the mechanism by which DPR im-
proves organ blood flow is not mediated exclusively through direct
contact. Examination of serum cytokine levels in sham (no hem-
orrhage), CR, and DPR animals revealed that inflammatory cyto-
kines such as IL-1a, IL-1b, and IL-6, were increased in CR animals
and equivalent to sham animals in the DPR group after hemorrhagic
shock. Inflammatory mediator IFN-g was increased in CR and DPR
animals compared to sham, and anti-inflammatory IL-10 was
reduced in CR and DPR animals [11]. Similar results were seen in
the ABD model, where pro-inflammatory cytokines IL-1a, IL-1b, IL-
6, IFN-g, and IL-18 were reduced in the DPR group compared to the
groups which received IVF alone [13].
Tissue damage also leads to the release of damage-associated
molecular patterns (DAMPs). This is a diverse group of molecules
which act much like external pathogens, activating the same toll-
 J.L. Weaver, J.W. Smith / International Journal of Surgery 33 (2016) 237e241
Fig. 2. Use of DPR prevents a reduction in hepatic blood flow compared to CR (BL ¼ baseline, HEM ¼ hemorrhage, PR ¼ post-resuscitation).
like receptors that ramp up the body's inflammatory response [14].
Serum hyaluronic acid and High-Mobility Group Box 1 (HMGB-1)
protein levels, which are markers of cellular injury, were elevated in
the CR group and become equivalent to shams with the addition of
DPR. Hyaluronic acid forms a part of tight junctions. HMGB-1 is
normally sequestered in the nucleus due to its paracrine inflam-
matory properties, and thus finding it in the cytosol is a sign of
tissue damage. Immunohistochemistry staining showed that in
sham and DPR animals HMBG-1 remained contained in the nu-
cleus, while in CR animals it migrated to the cytosol (Fig. 3). Levels
of pro-inflammatory lipopolysaccharide (LPS) were increased in CR
compared to both DPR and sham animals [11].
The fact that different cytokines responded differently to the
application of DPR suggests that the anti-inflammatory properties
of DPR are not global, but in fact act through specific inflammatory
pathways. The effects seen on tight junction proteins indicates that
not only does DPR reduce the production of inflammatory media-
tors, but also helps maintain the permeability of the intestine and
reduce the release of these inflammatory mediators into the
circulation.
7. Application in humans
In humans, we initially applied DPR to patients with an open
abdomen after laparotomy for trauma or intra-abdominal sepsis. To
perform this, the tubing from a 19F Jackson-Pratt (JP) drain is
inserted through the abdominal wall and the internal end placed
around the base of the mesentery. The abdomen is then tempo-
rarily closed with a vacuum device. We typically use an improvised
vacuum-assisted closure device (Barker type) including an under-
lay of perforated sterile plastic sheeting, blue towels, two chest
tubes, and an adherent dressing such as an Ioban (see Fig. 4). A good
seal with the adherent dressing is essential to maintain suction and
prevent the fluid from leaking. The chest tubes are connected to
each other and to suction using a Y connector. Chest tubes should
be at least 28F and the bowel must be protected from the suction
ports on the tubes. The PD solution is infused through the JP tubing
at 800 cc/hr for the first hour and then continuously lavages the
abdomen at 400 cc/hr. The chest tubes are kept to continuous wall
suction. We have found the 2.5% glucose-based PD solution to be
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239
the most effective, even when compared to more hypertonic so-
lutions, which tended to desiccate the tissue and pull fluid from the
intravascular space [9,15]. The DPR solution should be warmed to
37  C to avoid inducing hypothermia.
In patients without an open abdomen, the access is inserted at
the bedside or at the time of operation. A small incision is made
below the umbilicus and a commercially-available Diagnostic
Peritoneal Lavage catheter is inserted using the open Seldinger
technique. One liter of PD fluid is instilled over an hour utilizing
either gravity or a bedside IV pump. The fluid is left in the abdomen
for an hour, and then allowed to drain via gravity over an hour. This
sequence is repeated during acute resuscitation. Higher infusion
volumes should be avoided due to the risk of abdominal
compartment syndrome in the closed abdomen.
8. Results of human studies
Use of DPR has expanded into human studies and shown
numerous benefits. A retrospective study demonstrated that use of
DPR after damage-control surgery for hemorrhagic shock decreased
the time to definitive abdominal closure, as well as increased the
rate of primary fascial closure. Rates of significant complications,
such as enterocutaneous fistula and abdominal hernia were also
reduced, likely due to the improved fascial closure rate [16]. While
resuscitation practices in trauma patients have changed since the
publication of that manuscript, these initial efforts produced
promising results. Additionally, the use of DPR following abdominal
catastrophes has also shown an improvement in time to abdominal
closure and primary fascial closure rate, as well as reduced venti-
lator days and ICU length of stay when compared to propensity-
matched controls [17]. Most recently, we have demonstrated that
use of DPR in brain dead organ donors improves the organ pro-
curement rate per donor, particularly by increasing lungs procured,
likely due to reduced edema and improved blood flow [18].
9. Future directions
Further experiments will continue to explore the potential
benefits and applications of DPR. While we have demonstrated
reduced levels of inflammatory cytokines, we have not yet shown
240 J.L. Weaver, J.W. Smith / International Journal of Surgery 33 (2016) 237e241

Fig. 3. Left: Hepatic H&E staining showing increased cellular edema with CR and preserved cell architecture with DPR. Right: Immunohistochemistry staining in liver showing
migration of HMGB-1 into the cytosol after CR and maintenance of HMGB-1 in the nucleus with DPR.

whether this translates to changes in leukocyte activity, especially

the infiltration of macrophages and neutrophils into organs. Ex-
periments to explore this relationship are ongoing. Also, we have
only used commercially-available hypertonic fluid for DPR, and
addition of other compounds to the fluid could cause additional
changes to the post-resuscitation physiology seen after shock.
Finally, within our organ donor patients, the need for organ out-
comes follow-up continues to investigate if DPR improves organ
function in organ recipients.

Ethical approval

Not Applicable, study is a review.

Author contribution

JW: wrote manuscript; JS: edited manuscript.

Sources of funding

Fig. 4. Set-up for continuous DPR in patients with an open abdomen. None.

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 J.L. Weaver, J.W. Smith / International Journal of Surgery 33 (2016) 237e241
Conflicts of interest
None.
Guarantor
Jason W Smith MD PhD.
References
[1] D.S. Gann, W.R. Drucker, Hemorrhagic shock, J. Trauma Acute Care Surg. 75 (5)
(2013) 888e895.
[2] B. Abou-Khalil, et al., Hemodynamic responses to shock in young trauma
patients: need for invasive monitoring, Crit. Care Med. 22 (4) (1994) 633e639.
[3] J. Chen, et al., Estrogen prevents intestinal inflammation after trauma-
hemorrhage via downregulation of angiotensin II and angiotensin II subtype
I receptor, Am. J. Physiol. Gastrointest. Liver Physiol. 295 (5) (2008)
G1131eG1137.
[4] H.T. Hassoun, et al., Post-injury multiple organ failure: the role of the gut,
Shock 15 (1) (2001) 1e10.
[5] P. Scaffidi, T. Misteli, M.E. Bianchi, Release of chromatin protein HMGB1 by
necrotic cells triggers inflammation, Nature 418 (6894) (2002) 191e195.
[6] C.J. Carrico, et al., Multiple-organ-failure syndrome, Arch. Surg. 121 (2) (1986)
196e208.
[7] R.N. Garrison, et al., Direct peritoneal resuscitation as adjunct to conventional
resuscitation from hemorrhagic shock: a better outcome, Surgery 136 (4)
(2004) 900e908.
Downloaded for Anonymous User (n/a) at KAISER PERMANENTE from ClinicalKey.com by Elsevier on February 13, 2021.
For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.
241
[8] F.N. Miller, et al., Hyperosmolality, acetate, and lactate: dilatory factors during
peritoneal dialysis, Kidney Int. 20 (3) (1981) 397e402.
[9] R. Zakaria el, et al., Generalized dilation of the visceral microvasculature by
peritoneal dialysis solutions, Perit. Dial. Int. 22 (5) (2002) 593e601.
[10] R. Zakaria el, et al., Intraperitoneal resuscitation improves intestinal blood
flow following hemorrhagic shock, Ann. Surg. 237 (5) (2003) 704e711 dis-
cussion 711e3.
[11] J.L. Weaver, et al., DPR reduces visceral ischemia and inflammatory cytokines
following hemorrhagic shock, in: Academic Surgical Congress, 2014 (Las
Vegas, NV).
[12] R. Zakaria el, et al., A novel method of peritoneal resuscitation improves organ
perfusion after hemorrhagic shock, Am. J. Surg. 186 (5) (2003) 443e448.
[13] J.W. Smith, et al., Direct peritoneal resuscitation improves inflammation, liver
blood flow, and pulmonary edema in a rat model of acute brain death, J. Am.
Coll. Surg. 219 (1) (2014) 79e87.
[14] H.J. Anders, L. Schaefer, Beyond tissue injury-damage-associated molecular
patterns, toll-like receptors, and inflammasomes also drive regeneration and
fibrosis, J. Am. Soc. Nephrol. 25 (7) (2014) 1387e1400.
[15] R. Zakaria el, et al., Vasoactive components of dialysis solution, Perit. Dial. Int.
28 (3) (2008) 283e295.
[16] J.W. Smith, et al., Direct peritoneal resuscitation accelerates primary abdom-
inal wall closure after damage control surgery, J. Am. Coll. Surg. 210 (5) (2010)
658e664, 664e7.
[17] J.W. Smith, et al., Adjunctive treatment of abdominal catastrophes and sepsis
with direct peritoneal resuscitation: indications for use in acute care surgery,
J. Trauma Acute Care Surg. 77 (3) (2014) 393e398 discussion 398e9.
[18] J.W. Smith, et al., Addition of direct peritoneal lavage to human cadaver organ
donor resuscitation improves organ procurement, J. Am. Coll. Surg. 220 (4)
(2015) 539e547.